32578_Management of DVT

8/22/2019 32578_Management of DVT

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Management of DVT

Soheir Adam, MD, MSC, FRCPath

Asst. Professor & Consultant

Hematologist KAU


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VTE

Incidence of VTE 2-3 per 1000

Incidence is higher in men than in

women ( above the age of 45).Overall adjusted incidence in men is

130 : 100,000 vs 110: 100,000 inwomen(1.2:1)


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VTE

DVT and PE are a single clinical entity

Risk of early death in DVT + PE is 18 X higherthan in DVT alone

of PE cases present with sudden death

Other predictors of poor survival in DVT areolder age, male gender, confinement tohospital, CHF, chronic lung disease,neurological disease and active malignancy.


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3. Thrombus formation in the left auricle

(computer graphics superimposed on in-body

photograph)

The irregular beating of the heart in atrial fibrillation

creates ideal conditions for thrombus formation in the

left auricle, especially in patients with mitral valve

insufficiency.


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5. Fragmentation of the thrombus

(computer graphics superimposed on in-body

photograph)

As the size of the thrombotic mass increases, it

becomes more of a threat. Especially if the heart rate is

normalised, fragments of the thrombus may break away

to be swept into the circulation.


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PE

Predictors of poor survival in PE:

Syncope

Arterial hypotensionRight sided HF ( clinically or by plasma

markers levels or echocardiography)

These should receive aggressiveanticoagulation +/- thrombolytic therapy.


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11. Diagnosis of pulmonary embolism

(perfusion and ventilation scans)

In another patient with pulmonary embolism,a perfusion scan shows that an embolus hasstopped the blood flow to part of one lung.The ventilation scan shows that this area

is ventilated normally.


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Long Term Complications of

VTERecurrence

PTS


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Complications of VTE

1. Recurrence

Prandoni et al found the risk aftercessation of anticoagulation 24.8% at 5years and 30.3% at 8


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14. Ref: Schulman S et al. The duration of oral anticoagulant therapy after asecond episode of venous thromboembolism. The Duration of Anticoagulation

Trial Study Group. N Engl J Med 1997;336:393-8Short-term primary prevention of deep vein thrombosis/pulmonary embolism withanticoagulant therapy is today common practice for patients undergoing orthopaedicsurgical procedures. Patients with confirmed deep vein thrombosis, irrespective of theunderlying cause, typically receive anticoagulant treatment for 3 to 6 months, dependingon the location of the thrombosis and on other risk factors that the patient may have.

For pulmonary embolism the duration of treatment is often 6 months. However, theoptimal length of therapy is the subject of debate. Patients are at increased risk ofsuffering from a new episode of venous thromboembolism once anticoagulant therapyis completed. The next embolus may well prove to be fatal. There is a marked differencein the cumulative probability of a new episode of venous thromboembolism between thepatients receiving indefinite treatment and those in the 6-month group.


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Risk of recurrence increased with

Male gender

Increased age

Increased BMI Neurological disease

Paresis

Active malignancy

Idiopathic VTE

APS Prt C,S and AT deficiency

Persistent residual DVT

Consider pro longed 2ry proph ylaxis in the above


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Factors not predictive of recurrence:

VTE in pregnancy, CCP and gynecologicalsurgery

Recent surgery, trauma or fracture.

Recent immobilzation

Hormonal therapy (Tamoxifen)

Failed prophylaxis Distal DVT, deep muscular DVT

Short term oral ant icoagulat ion considered


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Recurrent PE

Risk of 7 day case mortality is significantly higher(34%) in recurrent PE, compared to recurrent

DVT(4%) aloneConsider prolonged anticoagulation, especially if

compromised cardiopulmonary functions


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Complications of DVT

2- Post- thrombotic syndrome

Develops in 20- 30% of DVT

Valvular damage or scarring leading toincompetence / residual venous obstruction dueto incomplete clearance

Systemic thrombolytic therapy wasnt found to

reduce incidence of PTS. Catheter- directed thrombolysis may hold

potential but not recommended routinely.


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Complications of DVT

Risk factors for PTS

Inadequate initial anticoagulation

Recurrent DVTHigher BMI

Distal vein thrombosis

Recently, persistently elevated D- dimersNot impact for long term anticoagulation.


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Impact of PTS

In the US $ 200,000,000 annually totreat PTS and 2 million work days lost

In Sweden its 75% of cost of DVT ttt In developing world major morbidity

Poorer QOL


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16. Post-thrombotic syndrome; leg ulcer

Considerable numbers of patients suffer from post-thromboticsyndromes with, in severe cases, leg ulcers. Venousthromboembolism is an underestimated disease with hugesocio-economic implications.


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Management of VTE

Aim of Management:

Initially : to prevent propagation of

thrombusChronic anticoagulation to allow

fibrinolysis and recanalization.


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Management of VTE

Heparin immediately and for at least 5days

VKA started on the 1st day Failure to achieve optimum treatment

early on leads to recurrence rates of

20 %


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Haemostasis: generation of thrombin and clot formation


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Management of VTE

UFH vs. LMWH

Pros:

Similar efficacy &superior safety

Monitoring

Risk of bleeding (lower risk in LMWH 1.3% vs.2.1%, odds ratio 0.60, meta-analysis of 14 studies)

Lower overall mortality ( cancer pts.)

Outpatient management

Overall cost


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Table 1 Recurrent symptomatic venous thromboembolism (VTE), major bleeding and mortality at

3 months summary of two meta-analyses in deep vein thrombosis and pulmonary embolism

Low molecular weight

heparin (%)

Unfractionated

heparin (%)

OR (95% CI)

Deep vein thrombosis

Recurrent VTE 86/1998 (4.3) 113/2021 (5.6) 0.75 (0.551.01)

Major bleeding 30/2353 (1.3) 51/2401 (2.1) 0.60 (0.390.93)

Mortality 135/2108 (6.4) 172/2137 (8.0) 0.78 (0.620.99)

Pulmonary embolism

Recurrent VTE 30/988 (3.0) 39/895 (4.4) 0.68 (0.421.09)

Major bleeding 14/1023 (1.4) 21/928 (2.3) 0.67 (0.361.27)

Mortality 46/988 (4.7) 55/895 (6.1) 0.77 (0.521.15)


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Management of VTE

LMWH

Cons

Reversal in bleeding patients: only the ATactivity, not the Xa is neutralized

Obese patients: adjusted vs. total bodyweight

Renal failure


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Indirect thrombin inhibition

Heparin/antithrombin/thrombin complex

Heparin

Antithrombin

Thrombin


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Management of PE

UFH gradually replaced by LMWH

Similar efficacy and safety in sub-

massive PENo difference in mortality between

altepase and LMWH compared toLMWH alone (NEJM 2002)

Thrombolytic therapy essential inmassive PE (better identification ofpatients needed).


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Table 2 Subgroup analysis of trials that included major (hemodynamically unstable) pulmonary embolismcompared with those that excluded patients with major pulmonary embolism

Outcome

Trials that included patients with major

PE

Trials that excluded patients with

major PE

Lysis, n/N

(%)

Heparin,

n/N(%)

OR (95% CI) Lysis,

n/N(%)

Heparin,

n/N(%)

OR (95% CI)

Recurrent

PE or death

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(9.4)

24/126

(19.0)

0.45 (0.22

0.92)

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(5.3)

12/248

(4.8)

1.07 (0.50

2.30)

Recurrent

PE

5/128 (3.9) 9/126 (7.1) 0.61 (0.23

1.62)

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(2.0)

7/248 (2.8) 0.76 (0.28

2.08)

Death 8/128 (6.2) 16/126

(12.7)

0.47 (0.20

1.10)

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(3.3)

6/248 (2.4) 1.16 (0.44

3.05)

Major

bleeding

28/128

(21.9)

15/126

(11.9)

1.98 (1.00

3.92)

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(2.4)

8/248 (3.2) 0.67 (0.24

1.86)

Wan et al, Circulat ion 2004.

Thrombolytic Therapy in PE


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Outpatient Management of

DVT

Hospital admissions

Reduce the length of waiting time in A/E Pressure on hospital beds

Cost issues


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Exclusion Criteria

Co- existent serious medical pathology

Severe acute venous obstruction

Patients in significant pain Renal impairment creatinine > 200 mol/l

Liver disease

Communication problems

Poor social background Limited mobility

Active bleeding


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Exclusion Criteria

High risk of bleeding

Active peptic ulcer Uncontrolled hypertension ( diastolic> 110mmHg,

systolic >200mmHg)

Angiodysplasia

Recent CNS or eye surgery Recent hemorrhagic stroke

Thrombocytopenia ( plts < 100 X109/ L)


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Clinical Assessment for DVT

Suitable for OutpatientManagement

Yes No

DVT confirmed

Patient analgesia

Support stocking

Medical assessment

Need for medical follow- up

Refer to hemostasis nurse

Anticoagulant treatment

Liaise with general practitioner

Yes No


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Outpatient Diagnosis

No undue delay

Validated clinical probability scores and

3rd

generation D- dimer assays If indicated then radiological

investigations will follow ( vacant slots forA/E )

Diagnosis usually responsibility ofmedical team, A/E team


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Clinical Prediction Rule

Entire leg tenderness along deep veins

Collateral superficial veins

Entire leg swelling

Calf swelling >3 cm difference Dilated superficial veins

Pitting edema

Recent bed ridden >3 days

Major surgery within last 3 ms.

Active cancer within last 6 mo. Plaster

Paralysis

Presence of alternative Diagnosis


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Imberti et al, 2006

Journal of Thrombosis

& Haemostasis


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Outpatient Management

Under auspices of HematologyDepartment

One of several scenarios Daily OPD attendance

District nurse or outreach hemostasisnurse

LMWH administered by GP

Administered by patient or relative


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Lines of Accountability inOutpatient Management of DVT

Diagnostic team

Investigation of initial DVT/ PE

Investigation of recurrent DVT/PE Patient analgesia

Assessment for ambulatory care

Formal medical assessmentMedical follow- up

Liaison with GP


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Lines of Accountability inOutpatient Management of DVT

Treatment team

Administration of outpatient care

program Support stockings

Patient education

Thrombophilia testingAnticoagulant therapy

Liaison with GP


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Vitamin K Antagonists

> reduction of risk of recurrence

Bleeding risk is 1.4% per year of major

bleeds 0.25% of fatal bleeds per year


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Vitamin K Antagonists

Inhibits Vitamin K dependentcarboxylase activity

Prevents reduction of Vitamin K

Humans secrete des--carboxyglutamicacid, an inactive protein

Does not affect proteins already

synthesizedMonitoring

Multiple interactions with other drugs


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Duration of Anticoagulation

Plan designed clearly for each patientindividually at the start of anticoagulation

Long term treatment of deep vein thrombosis (DVT) and pulmonary


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Long-term treatment of deep vein thrombosis (DVT) and pulmonary

embolism (PE)*

Patient categories Dru

g

Duration

(months)

Comments

First episode of DVT or PEsecondary to a transient

(reversible) risk factor

VKA

3 Recommendation applies to bothproximal and calf vein thrombosis

First episode of idiopathic DVT or

PE

VK

A

612 Continuation of anticoagulant

therapy after 612 months may be

considered

First episode of DVT or PE and

cancer

LM

WH

36 Continuation of LMWH is

recommended indefinitely or until

the cancer is resolved

First episode of DVT or PE with a

documented thrombophilic

abnormality

VK

A



considered

First episode of DVT or PE with

documented antiphospholipid

antibodies or two or more

thrombophilic abnormalities

VK

A



considered

VKA, vitamin K antagonist; LMWH, low molecular weight heparin.

*Based on the Seventh ACCP Conference document (13).


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Duration of

ThromboprophylaxisIndef in i te ant icoagu lat ion recommended :

Two or more spontaneous thromboses

One spontaneous thrombosis in case of AT deficiency orthe APS

One life- threatening thrombosis

One spontaneous thrombosis at an unusual site

One spontaneous thrombosis in the presence of multiplegenetic thrombophilia defects


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BSH guidelines 2005


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Prevention of Recurrent VenousThromboembolism (PREVENT)

Closed in December 2002

Low intensity Warfarin reduced the

rate of recurrence by 60% compared toplacebo

No increase in major bleedingcomplications


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Management of Thrombophilia

AT deficiency

Some patients are resistant to Heparin

AT conc hasnt been studied in a controlled trial

as an alternative to Heparin

AT conc. can be used safely and effectively inAT deficiency and

Acute severe VTE

Difficulty to achieve adequate anticoagulation

Recurrent thrombosis despite adequateanticoagulation


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Protein C Deficiency

Oral anticoagulation started under cover ofHeparin

Dose of OAC should be gradually increased

from 2mg for 3/7 until desired INR is reached

WISN is an uncommon complication due to atransient hypercoagulable status

Protein C conc. Can be used for prophylaxis

against recurrent skin necrosis


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32578_Management of DVT